1. Field of the Invention
The invention relates generally to the fields of immunology and inflammatory bowel disease and more specifically to the diagnosis and treatment of a clinical subtype of ulcerative colitis.
2. Background Information
Inflammatory bowel disease (IBD) is the collective term used to describe two gastrointestinal disorders of unknown etiology: Crohn's disease (CD) and ulcerative colitis (UC). The course and prognosis of ulcerative colitis, which occurs world-wide and is reported to afflict as many as two million people, varies widely. Onset of ulcerative colitis is predominantly in young adulthood with diarrhea, abdominal pain, and fever the three most common presenting symptoms. The diarrhea may range from mild to severe and often is accompanied by bleeding. Anemia and weight loss are additional common signs of UC. Ten percent to fifteen percent of all patients with inflammatory bowel diseases such as UC will require surgery over a ten year period. In addition, patients with UC are at increased risk for the development of intestinal cancer. Reports of an increasing occurrence of psychological problems, including anxiety and depression, are perhaps not surprising symptoms of what is often a debilitating disease that strikes people in the prime of life.
Unfortunately, the available therapies for ulcerative colitis are few, and both diagnosis and treatment have been hampered by a lack of knowledge regarding the etiology of the disease. What is clear, however, is that the pathogenesis of ulcerative colitis involves immune-mediated damage to the intestinal mucosa. Autoantibodies, specifically antibodies against cytoplasmic components of neutrophils (pANCA), have been reported in 68–80% of patients with ulcerative colitis, further supporting a role for immune dysregulation in this disease. However, the antigens recognized by these pANCA autoantibodies, which would be useful in diagnosing and treating UC patients have, to date, escaped identification.
In other inflammatory bowel diseases such as Crohn's disease, bacteria have been implicated in the initiation or progression of the disease. That microbes can play a role in Crohn's disease is supported, for example, by the efficacy of antibiotics and diet in mitigating disease in some Crohn's patients. However, until now a role for microbes or microbial antigens in the immune dysregulation producing UC has not been suspected. Such microbial antigens can be the original inducers of the disease-related immune response in UC and, as such, can contain displayed B-cell epitopes that react especially effectively with UC pANCA autoantibodies. As a consequence, these microbial antigens can increase the level of UC serodetection from its current level of 60–70% with the fixed neutrophil assay. Such microbial antigens also can bear a disease related T-cell epitope and, as likely original inducers of the disease-related immune response, can be particularly effective tolerogenic antigens for treating UC patients.
Thus, there is a need for identification and isolation of UC pANCA target antigens, including antigens of microbial origin such as those expressed in colonic bacteria of UC patients. Such antigens would be useful for diagnosing and treating the large population of UC patients that have pANCA autoantibodies. The present invention satisfies this need by providing the histone Hi UC pANCA target antigen and additional UC pANCA microbial antigens. Related advantages are provided as well.